Spleen cells from animals tolerant to a thymus-dependent antigen can be activated by lipopolysaccharide to synthesize antibodies against the tolerogen.

Abstract

Immunological tolerance was induced in adult mice by the injection of 5 mg of deaggregated hapten-protein [fluorescein isothiocyanate human .gamma.-globulin] conjugate. The tolerant state was confirmed 4-19 days later by the failure of such animals to mount an immune response against an aggregated form of the same thymus-dependent (T) hapten-protein conjugate and by the inability of spleen cells from tolerant animals to respond to a thymus-independent haptein-carrier conjugate. Even though the animals were fully tolerant, their spleen cells were activated by [Escherichia coli] lipopolysaccharide (LPS) in vitro to produce normal numbers of plaque-forming cells against the hapten. The finding that spleen cells from tolerant animals could be activated by LPS into synthesis of antibodies against the tolerogen indicates that tolerance to T antigens does not affect B [bone marrow-derived] cells, but presumably only T cells. The only stringent test for the existence of B-cell tolerance is apparently the inability of polyclonal B-cell activators to activate antibody synthesis against the tolerogen. B-cell tolerance to autologous T antigens probably does not exist; such antigens apparently cannot deliver activating or tolerogenic signals to B cells, although they are competent to combine with and block the Ig[immunoglobulin] receptors.